Determination of chemical composition and isotope distribution with mass spectrometry

Abstract

A method for determining elemental composition of ions from mass spectral data, comprising obtaining at least one mass measurement from mass spectral data; obtaining a search list of candidate elemental compositions whose exact masses fall within a given mass tolerance range from the accurate mass; reporting a probability measure based on a mass error; calculating an isotope pattern for each candidate elemental composition from the search list; constructing a peak component matrix including at least one of the isotope pattern and mass spectral data; performing a regression against at least one of isotope pattern, mass spectral data, and the peak component matrix; reporting a second probability measure for at least one candidate elemental composition based on the isotope pattern regression; and combining the two the probability measures into an overall probability measure. A method for determining elemental isotope ratios from mass spectral data.

1. A method for determining elemental composition of ions from mass spectral data, comprising the steps of:
 obtaining at least one accurate mass measurement from mass spectral data obtained by using a mass spectrometer; 
 obtaining a search list of candidate elemental compositions whose exact masses fall within a given mass tolerance range from said accurate mass; 
 reporting a probability measure based on a mass error; 
 calculating, using a computer, an isotope pattern for each candidate elemental composition from said search list; 
 constructing a peak component matrix including at least one of said isotope pattern and mass spectral data; 
 performing a regression against at least one of isotope pattern, mass spectral data, and the peak component matrix; 
 reporting a second probability measure for at least one candidate elemental composition based on said isotope pattern regression; and 
 combining the two said probability measures into an overall probability measure through the use of probability multiplications. 
 
     
     
       2. The method of  claim 1 , where the isotope pattern has a desired peak shape function. 
     
     
       3. The method of  claim 2 , where the desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function. 
     
     
       4. The method of  claim 2 , where the isotope pattern is a linear combination of at least two ions. 
     
     
       5. The method of  claim 4 , where the at least two ions include native and isotope labeled versions of the ion. 
     
     
       6. The method of  claim 1 , where the measured mass spectral response has been calibrated to have a desired peak shape function. 
     
     
       7. The method of  claim 6 , where a desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function from a mass spectral calibration involving peak shape. 
     
     
       8. The method of  claim 1 , where the isotope pattern is theoretically calculated through the convolution of isotope distribution and a desired peak shape function. 
     
     
       9. The method of  claim 8 , where a desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function from a mass spectral calibration involving peak shape. 
     
     
       10. The method of  claim 8 , where the isotope distribution is theoretically calculated from at least one elemental composition. 
     
     
       11. The method of  claim 8 , where an elemental composition is obtained through a search of possible elemental compositions using the measured mass spectral response. 
     
     
       12. The method of  claim 1 , where the peak component matrix contains baseline components which are at least one of linear and nonlinear in nature. 
     
     
       13. The method of  claim 1 , where the peak component matrix contains first derivative of at least one of the measured mass spectral response and an isotope pattern already included in the peak component matrix. 
     
     
       14. The method of  claim 1 , where the peak component matrix contains at least one of the isotope pattern and its first derivative of any interfering ions. 
     
     
       15. The method of  claim 1 , where the regression is a multiple linear regression. 
     
     
       16. The method of  claim 1 , where the regression is a weighted regression. 
     
     
       17. The method of  claim 16 , where the weights are all ones. 
     
     
       18. The method of  claim 16 , where the weights are inversely proportional to the mass spectral variance. 
     
     
       19. The method of  claim 18 , where the mass spectral variance is proportional to the mass spectral intensity. 
     
     
       20. The method of  claim 1 , where the probability measure is a p-value. 
     
     
       21. The method of  claim 1 , where an overall p-value is derived as the product of two independent p-values. 
     
     
       22. The method of  claim 21 , where all candidate elemental compositions in said search list are ranked based on said overall probability measure. 
     
     
       23. The method of  claim 1 , where an estimated standard deviation is reported for said accurate mass measurement. 
     
     
       24. The method of  claim 1 , where the mass tolerance range is derived as a function of an estimated standard deviation in the accurate mass measurement. 
     
     
       25. The method of  claim 1 , where said probability measure based on mass error is established based on estimated standard deviation of the accurate mass measurement. 
     
     
       26. The method of  claim 1 , where the peak component matrix is updated and regression repeated by adding or deleting components in the matrix. 
     
     
       27. The method of  claim 26 , where adding or deleting components is based on probability measures obtained from a regression. 
     
     
       28. The method of  claim 1 , where a mass axis has been transformed through one of linear and nonlinear functions. 
     
     
       29. A computer programmed with non-transitory computer code for performing the method of  claim 1 . 
     
     
       30. The computer of  claim 29 , in combination with a mass spectrometer for obtaining mass spectral data to be analyzed by said computer to determine elemental composition of ions from said mass spectral data. 
     
     
       31. A non-transitory computer readable medium having computer readable instructions stored therein for causing a computer processor to perform the method of  claim 1 . 
     
     
       32. A mass spectrometer having associated therewith a computer for performing data analysis functions of data produced by the mass spectrometer, the computer performing the method of  claim 1  to determine elemental composition of ions from said mass spectral data. 
     
     
       33. A method for determining elemental isotope ratios directly from mass spectral data, comprising the steps of:
 obtaining measured mass spectral response, said measured mass spectral response obtained by using a mass spectrometer; 
 specifying the elemental composition of a given ion; 
 specifying the initial isotope ratios for a given element in the ion; 
 calculating, using a computer, the isotope pattern for said ion; 
 constructing a peak component matrix including at least one of said isotope pattern and measured mass spectral response; 
 performing a regression between measured mass spectral response and the peak component matrix; and 
 reporting a regression residual and repeating the isotope pattern calculation, peak component construction, and regression process with updated isotope ratios to minimize this residual. 
 
     
     
       34. The method of  claim 33 , where the isotope pattern has a desired peak shape function. 
     
     
       35. The method of  claim 34 , where the desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function. 
     
     
       36. The method of  claim 33 , where the measured mass spectral response is calibrated to have a desired peak shape function. 
     
     
       37. The method of  claim 36 , where a desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function from a mass spectral calibration involving peak shape. 
     
     
       38. The method of  claim 33 , where the isotope pattern is theoretically calculated through the convolution of isotope distribution and a desired peak shape function. 
     
     
       39. The method of  claim 38 , where a desired peak shape function is one of assumed peak shape function, actual peak shape function as one of measured and calculated, and target peak shape function from a mass spectral calibration involving peak shape. 
     
     
       40. The method of  claim 33 , where the peak component matrix contains baseline components which are at least one of linear and nonlinear in nature. 
     
     
       41. The method of  claim 33 , where the peak component matrix contains first derivative of at least one of the measured mass spectral response and an isotope pattern already included in the peak component matrix. 
     
     
       42. The method of  claim 33 , where the peak component matrix contains at least one of the isotope pattern and its first derivative of any interfering ions. 
     
     
       43. The method of  claim 33 , where the regression is a multiple linear regression. 
     
     
       44. The method of  claim 33 , where the regression is a weighted regression. 
     
     
       45. The method of  claim 44 , where weights for the regression are all ones. 
     
     
       46. The method of  claim 44 , where weights for the regression are inversely proportional to the mass spectral variance. 
     
     
       47. The method of  claim 46 , wherein mass spectral variance is proportional to mass spectral intensity. 
     
     
       48. The method of  claim 33 , where the peak component matrix is updated and regression repeated by adding or deleting components in the matrix. 
     
     
       49. The method of  claim 48 , where adding or deleting components is based on probability measures obtained from a regression. 
     
     
       50. The method of  claim 33 , where a mass axis has been transformed through one of linear and nonlinear functions. 
     
     
       51. A computer programmed with non-transitory computer code for performing the method of  claim 33 . 
     
     
       52. The computer of  claim 51 , in combination with a mass spectrometer for obtaining mass spectral data to be analyzed by said computer to determine elemental isotope ratios from said mass spectral data. 
     
     
       53. A non-transitory computer readable medium having computer readable instructions stored therein for causing a computer processor to perform the method of  claim 33 . 
     
     
       54. A mass spectrometer having associated therewith a computer for performing data analysis functions of data produced by the mass spectrometer, the computer performing the method of  claim 33  to determine elemental isotope ratios from said mass spectral data.